Elsevier

Drug and Alcohol Dependence

Volume 57, Issue 1, 1 November 1999, Pages 69-78
Drug and Alcohol Dependence

A multivariate genetic analysis of the use of tobacco, alcohol, and caffeine in a population based sample of male and female twins

https://doi.org/10.1016/S0376-8716(99)00053-8Get rights and content

Abstract

Numerous epidemiologic studies in the past few decades have consistently demonstrated positive associations between the use of various psychoactive substances, both licit and illicit. This association could be due to shared genetic and/or shared environmental risk factors. This study uses multivariate structural equation modeling to determine the sources of covariation between the use of tobacco, alcohol, and caffeine, the three most commonly consumed psychoactive substances. In particular, we wish to clarify the extent to which genetic and environmental risk factors are shared across these three substances versus are substance specific in their effect. The sample, consisting of data collected from members of the population-based Virginia Twin Registry, consists of 774 monozygotic and 809 dizygotic male and female twin pairs. Our results demonstrate that genetic and individual specific environmental factors that are shared between these three substances account for a modest proportion of the total variance. For example, shared genetic risk factors across the three substances in males and females account for between 7 and 28% of the total variance in liability and 12–56% of the genetic variance. Common familial environment appears to play little or no role. Underlying genetic and individual environmental risk factors produce liability to (poly)substance use in general; substance specific factors also play an important etiologic role.

Introduction

Historically, associations between the use of various psychoactive substances have been consistently demonstrated (Istvan and Matarazzo, 1984; Kozlowski et al., 1993). Since most studies have found a substantial heritability for the risk of using any one substance (Hughes, 1986; Carmelli et al., 1990), genetic models for polysubstance use have been postulated to account for this association. One prevailing hypothesis is that there is a general non-specific underlying genetic risk factor that increases one’s liability to use multiple psychoactive substances. This general genetic liability might be due to variation in genetically influenced personality traits that impact on drug use such as sensation seeking (Zuckerman, 1994) or variation in the biological substrates, such as the basal forebrain dopamine system, that may influence the hedonic effect for many substances of abuse (Leschner, 1997; Wise, 1998). Another hypothesis proposes that genetic risk factors are largely substance specific, due, for example, to variation in receptor systems specific to individual drugs of abuse. Similarly, shared or substance specific environmental sources may be postulated to account for these behaviors. For example, overall predisposition to substance use may be etiologically related to such environmental factors as abuse history, peer group, etc., while use of a specific substance may be determined by exposure history, cost, and availability. Most previous behavior genetic studies of the use of individual psychoactive substances have demonstrated both genetic and environmental sources of liability.

As prototypical psychoactive substances, tobacco, alcohol, and caffeine are of interest for several reasons. First, these are widely consumed in this society (SAMHSA, 1996) and this high prevalence allows for significant statistical power in reasonably sized samples. Second, most studies in the past have suggested that the use of these substances is moderately heritable (Hughes, 1986; Carmelli et al., 1990). Furthermore, significant associations between use of these substances have been demonstrated in the past, suggesting commonality in an individual’s predisposition to their use (Istvan and Matarazzo, 1984). Several studies in recent years have looked at overlap in the use of these substances. For example, Swan et al. (1996) studied the consumption of tobacco, alcohol, and coffee in a population of World War II veteran male-male twin pairs. Looking at patterns of consumption also is a key step in understanding how genetic and environmental factors influence transitions from use to abuse and dependence (Heath et al., 1993; McGue, 1994; Kendler and Prescott, 1999). Abuse and dependence potential have been clearly established for alcohol, nicotine, and most probably, caffeine (Hughes et al., 1992; Strain et al., 1994). Most studies find substantial heritability estimates for alcoholism. The relationship between alcohol and nicotine dependence is only beginning to be unraveled (Prescott and Kendler, 1995). Because of the large public health burden attributable to alcohol and tobacco use, deeper understanding of the etiology of their use is crucial. In addition, some researchers postulate that there is a relationship between the use of these substances and that of illicit drugs (Kozlowski et al., 1993). Therefore, understanding the overlap of consumption of these legal psychoactive substances may provide a foundation for elucidating factors contributing to the use, abuse, and dependence of licit and illicit drugs plaguing our society.

This study looks at the genetic and environmental correlates for the consumption of the three most commonly consumed legal psychoactive substances: nicotine, alcohol, and caffeine. It utilizes the classical twin method in a population based sample of male and female same sex monozygotic and dizygotic twins and opposite sex dizygotic twins. We sought to answer several questions. Is the set of genes that predispose men to use psychoactive substances the same as for women? How specific are the genetic factors for the use of these common psychoactive substances? Are they relatively non-specific (one set of genes influencing them all) or highly specific (completely different sets of major genes)? Similarly, how specific or non-specific are the environmental factors for multiple substance use? Finally, is the pattern of multiple substance use due to genetic factors the same as that due to environmental factors, i.e. do they act in an independent manner or via a common pathway? One example of independently acting components would be if genes determined generic substance-related neural pathways but social circles influenced substance of choice. On the other hand, neurobehavioral models with genetic and environmental factors impacting upon potentially mediating personality measures would represent a common mechanism of action. A particular example would be the intermediate phenotypic trait of sensation seeking, which has roughly equal proportions of genetic and environmental liabilities (Zuckerman, 1994).

Section snippets

Sample population and data collection

Health history information was collected by questionnaire from members of the Virginia Twin Registry (Corey et al., 1991). The registry is based on the birth records of same-sex and opposite-sex twin pairs born in Virginia between 1915 and 1979. Health history information was solicited from those twins who agreed to participate by completing a preliminary zygosity determination questionnaire.

Zygosity determination was made on the basis of the responses made to three of 13 questions included in

Results

In substance abuse research, the validity of self-reported data on sensitive and stigmatized behaviors such as substance use has been of concern (Harrison and Hughes, 1997). In order to examine potential effects of cooperation bias on the representativeness of our sample, logistic regression analysis of the rates of survey return of pairs versus individuals was employed. Predictor variables included in the regression were zygosity, race, age, and substance use (tobacco, alcohol, and caffeine).

Discussion

We have examined the contributions of genetic and environmental factors to the use of tobacco, alcohol, and caffeine in a population based sample of male and female Caucasian twin pairs. Substantial univariate heritabilities for each of the three substances were obtained (Table 1): 49% (males) and 51% (females) for tobacco use; 60% (males) and 47% (females) for alcohol consumption; and 58% (males) and 58% (females) for caffeine consumption. In a review of previous twin studies, Hughes (1986)

Acknowledgements

We would like to thank Carol Williams for her assistance in accessing the Virginia Twin Registry database. This work was largely supported by NIH RO1 grants NS31564 and HD26746. K.S.K. is supported by an NIMH Research Scientist Award MH-01277.

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